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JAMA Diagnostic Test Interpretation

November 16, 2018

Serum Creatinine in the Critically Ill Patient With Sepsis

Matthieu Legrand, John A. Kellum

JAMA. Published online November 16, 2018. doi:10.1001/jama.2018.16627

Case 病例

73-year-old man underwent esophageal resection for cancer. He had a history of hypertension that was treated with an angiotensin receptor blocker. Preoperative estimated glomerular filtration rate (GFR) was 98 mL/min/1.73 m2. On the second postoperative day, body temperature was 38.6°C. Chest x-ray revealed bilateral lung consolidations consistent with pneumonia. Blood pressure decreased from 145/72 mm Hg to 96/53 mm Hg with a heart rate of 105/min. The patient was admitted to the intensive care unit (ICU) with acute respiratory failure and was placed on mechanical ventilation. In the ICU, urine output was 50 mL over 3 hours. On day 3, he received 4.5 L of Ringer lactate over 12 hours. Laboratory values are shown in the Table.

一名73岁男性患者因食道癌接受手术。患者既往有高血压病史,服用血管紧张素受体阻滞剂。术前评估GFR为98 mL/min/1.73 m2。在术后第2天,患者体温38.6°C。胸片显示双肺实变,符合肺炎表现。血压从145/72 mm Hg 下降到 96/53 mm Hg,心率105/min。患者因呼吸功能衰竭收入ICU并接受机械通气。入住ICU后3小时尿量为50 mL。第3天,患者在12小时内输注4.5 L乳酸林格氏液。实验室检查结果见下表。

问题:How Do You Interpret the Test Results From Day 3 Postoperatively at 3 am? 你如何解读术后第3天3AM的检查结果?

答案:B. The patient has acute kidney injury most likely related to sepsis. 患者的急性肾损伤很可能与全身性感染相关。

Tests Characteristics 检查特点

Serum creatinine is a marker of GFR. Serum creatinine level depends on creatinine production and elimination. Elimination mostly depends on GFR but tubular secretion is also important, especially in patients with markedly reduced kidney function. While muscle injury (ie, rhabdomyolysis) might increase creatine release, sepsis may decrease creatinine production such that serum creatinine may not increase despite a decrease in GFR. Serum creatinine increases slowly after acute kidney injury (AKI). Creatinine distributes in a large volume, approximating 60% to 70% of total body weight. The increase in serum creatinine is further delayed by administration of large amounts of fluid and positive fluid balance.1 For example, when patients with sepsis receive a large amount of fluids, AKI might be underrecognized.2 Reaching a steady state of serum creatinine level requires that all compartments in which creatinine distributes are at equilibrium between production and elimination. Current international consensus criteria for AKI include a relative increase in serum creatinine (≥50% from baseline within 7 days) or an absolute increase in serum creatinine (≥0.3 mg/dL within a 48-hour period).3 Mean Medicare reimbursement for serum creatinine testing is $5 to $6.

血清肌酐是GFR的标志物。血清肌酐水平取决于肌酐的产生与清除。肌酐的清除主要决定因素为GFR,但肾小管分泌也非常重要,尤其对于肾功能显著减退的患者。肌肉损伤(即横纹肌溶解)可能增加肌酐释放,全身性感染能够减少肌酐产生,因此,尽管GFR降低,但血清肌酐水平不一定升高。在急性肾损伤(AKI)发生后,血清肌酐缓慢升高。肌酐分布容积很大,几乎相当于体重的60-70%。输注大量液体以及液体正平衡可以进一步延缓血清肌酐水平的升高。例如,当全身性感染患者输注大量液体时,临床医生可能忽略AKI。血清肌酐水平达到稳态的前提是肌酐分布的所有间隙达到肌酐产生与清除的平衡。目前AKI的国际共识标准包括血清肌酐水平相对升高(7天内从基线水平增加≥50%)或血清肌酐水平的绝对增加(48小时内增加≥0.3 mg/dL)。Medicare针对血清肌酐检查的平均报销费用为$5 至 $6。

Application of the Test Results for This Patient 检查结果应用于本例患者

On postoperative day 3 at 3am, serum creatinine was only marginally increased despite AKI. Increased volume of distribution would be expected to lead to a decrease in serum creatinine level if the GFR was stable. The slight increase in serum creatinine, in this specific clinical context, led to early identification of AKI. Low urine output is also characteristic in AKI diagnosis (<0.5 mL/kg/h for more than 6 hours) and may precede the increase of serum creatinine. However, AKI can develop without oliguria, and 6-hour urine output monitoring is not always available, as in this case. The patient later met criteria for AKI stage 3 (ie, 3-fold increase in serum creatinine above baseline or ≥4 mg/dL). Early identification of AKI, however, allows for rapid identification of sepsis severity,4 which may facilitate earlier initiation of optimal care and avoidance of nephrotoxins (ie, vancomycin).5 It is important to recognize that AKI can develop in patients with sepsis, despite absence of arterial hypotension or shock.6

在术后第3天3AM,尽管患者已发生AKI,但血清肌酐水平仅轻度升高。如果GFR保持稳定,分布容积的增加可能导致血清肌酐水平的降低。在目前情况下,血清肌酐的轻度升高可以早期诊断AKI。尿量减少也是AKI的诊断标准(<0.5 mL/kg/h超过6小时),且可能先于肌酐升高出现。然而,AKI患者也可没有少尿表现,而且,正如此例患者,很多患者可能没有6小时尿量监测结果。此后患者符合AKI 3期诊断标准(即血清肌酐从基线值增加3倍或≥4 mg/dL)。早期鉴别AKI可有助于迅速确定全身性感染的严重程度,从而尽早开始适当治疗,避免使用肾毒性药物(如万古霉素)。认识到没有低血压或休克的全身性感染患者仍可以发生AKI,这一点非常重要。

What Are Alternative Diagnostic Testing Approaches? 其他诊断方法?

Cystatin C may be less affected by muscle mass and metabolism than creatinine, but it is not more sensitive to detect AKI than serum creatinine. Alternative biomarkers (eg, neutrophil gelatinase–associated lipocalin, insulin-like growth factor binding protein 7, and tissue inhibitor of metalloproteinases-2) can detect kidney damage and indicate impending AKI but do not directly measure GFR7 and should not replace serum creatinine. Urine analysis is important for some forms of AKI (eg, glomerular nephritis) but lacks sensitivity and specificity. Measuring creatinine clearance estimates GFR but requires a steady-state serum creatinine, urine creatinine, and precise urine volume measurement. Formulas have been proposed for correcting serum creatinine for fluid overload.8 In this case, correcting serum creatinine based on a positive fluid balance of 4.5 L and an estimated volume of distribution of 45 L (ie, 60% of 75 kg) indicated a corrected serum creatinine of 1.22 mg/dL at 3 am on day 3.

与肌酐相比,光抑素C较少收到肌肉量和代谢的影响,但其检测AKI的敏感性并不优于血清肌酐。其他生物标志物(如NGAL,胰岛素样生长因子结合蛋白7,和金属蛋白酶组织抑制剂-2等)也可检测肾损伤,对AKI作出预警,但并不直接反映GFR,因而不能替代血清肌酐。尿液分析对于某种类型的AKI(如肾小球肾炎)也非常重要,但缺乏敏感性和特异性。测定肌酐清除率可反映GFR,但要求血清肌酐水平处于稳态,同时需要精确测定尿肌酐及尿量。有很多公式用于液体负荷过多时对血清肌酐进行校正。对于本例患者,液体正平衡4.5 L,分布容积45 L(即75 kg的60%),校正后血清肌酐(第3天3AM)为1.22 mg/dL。

Patient Outcome 患者预后

The patient was diagnosed with postoperative pneumonia complicated by sepsis and AKI. The patient’s condition improved and he was discharged 23 days after admission to the ICU. At discharge, his serum creatinine was 0.7 mg/dL. Recovery can be overestimated because of muscle mass loss during an ICU stay and persistent positive fluid balance.9 Measured creatinine clearance was 72 mL/min/1.73 m2 over a 24-hour urine volume collection, reflecting partial recovery from AKI because the GFR had not reverted to baseline levels.10

患者确诊为术后肺炎并发全身性感染及AKI。收入ICU后第23天患者情况改善并出院。出院时,患者血清肌酐为0.7 mg/dL。由于在ICU住院期间肌肉量减少及持续液体正平衡,因此可能高估肾脏功能的恢复。通过收集24小时尿液标本,测定肌酐清除率为72 mL/min/1.73 m2,尚未完全恢复正常,反映肾脏功能仅有部分恢复。


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